Systematic in silico discovery of novel solute carrier-like proteins from proteomes.

Gyimesi, Gergely; Hediger, Matthias A (2022). Systematic in silico discovery of novel solute carrier-like proteins from proteomes. PLoS ONE, 17(7), e0271062. Public Library of Science 10.1371/journal.pone.0271062

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Solute carrier (SLC) proteins represent the largest superfamily of transmembrane transporters. While many of them play key biological roles, their systematic analysis has been hampered by their functional and structural heterogeneity. Based on available nomenclature systems, we hypothesized that many as yet unidentified SLC transporters exist in the human genome, which await further systematic analysis. Here, we present criteria for defining "SLC-likeness" to curate a set of "SLC-like" protein families from the Transporter Classification Database (TCDB) and Protein families (Pfam) databases. Computational sequence similarity searches surprisingly identified ~120 more proteins in human with potential SLC-like properties compared to previous annotations. Interestingly, several of these have documented transport activity in the scientific literature. To complete the overview of the "SLC-ome", we present an algorithm to classify SLC-like proteins into protein families, investigating their known functions and evolutionary relationships to similar proteins from 6 other clinically relevant experimental organisms, and pinpoint structural orphans. We envision that our work will serve as a stepping stone for future studies of the biological function and the identification of the natural substrates of the many under-explored SLC transporters, as well as for the development of new therapeutic applications, including strategies for personalized medicine and drug delivery.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Gyimesi, Gergely (A), Hediger, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Pubmed Import

Date Deposited:

29 Jul 2022 16:02

Last Modified:

29 Mar 2023 23:38

Publisher DOI:

10.1371/journal.pone.0271062

PubMed ID:

35901096

BORIS DOI:

10.48350/171626

URI:

https://boris.unibe.ch/id/eprint/171626

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